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13 - Platelet-derived growth factor

from Part 2.1 - Molecular pathways underlying carcinogenesis: signal transduction

Published online by Cambridge University Press:  05 February 2015

By
Arne Östman  and
Carl-Henrik Heldin
Edited by
Edward P. Gelmann ,
Charles L. Sawyers  and
Frank J. Rauscher, III
Arne Östman
Affiliation:
Cancer Center Karolinska, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
Carl-Henrik Heldin
Affiliation:
Ludwig Institute for Cancer Research, Uppsala University, Uppsala, Sweden
Edward P. Gelmann
Affiliation:
Columbia University, New York
Charles L. Sawyers
Affiliation:
Memorial Sloan-Kettering Cancer Center, New York
Frank J. Rauscher, III
Affiliation:
The Wistar Institute Cancer Centre, Philadelphia
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Summary

Introduction

Platelet-derived growth factor (PDGF) constitutes a family of disulfide-linked dimeric growth factors that promote cell growth and migration by activation of tyrosine kinase PDGFα- and β-receptors (1). PDGFs act predominantly on mesenchymal cells, such as fibroblasts, pericytes, and smooth muscle cells, and are also potent regulators of glial cells. In the context of tumor biology, PDGF isoforms act as autocrine factors for malignant cells, and as stimulators of fibroblasts and pericytes in the tumor stroma. Clinical studies have validated PDGF receptors, expressed on malignant cells or on cells of the tumor stroma, as relevant cancer drug targets (2).

Structure of PDGF and PDGF receptors

PDGF is a family of disulfide-bounded homodimers of homologous A-, B-, C-, and D-polypeptide chains. In addition, the A- and B-chains form a heterodimer PDGF-AB. The two subunits in the dimer are arranged in an anti-parallel manner, creating two symmetric receptor binding epitopes. The PDGF isoforms show sequence similarly to vascular endothelial cell growth factors (VEGFs). In addition, PDGFs, VEGFs, and transforming growth factor-β (TGF-β) show a similar folding with a cystine-knot structure (1).

Type
Chapter
Information
Molecular Oncology
Causes of Cancer and Targets for Treatment
 , pp. 135 - 143
Publisher: Cambridge University Press
Print publication year: 2013

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References

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